Human Participants and Sequencing

核心C，人类参与者和测序：摘要 在过去的十年中，遗传性原发性免疫缺陷（PID）的诊断率迅速上升 涉及T淋巴细胞功能障碍，部分原因是基于人群的新生儿筛查的出现， 严重联合免疫缺陷（SCID）。该计划项目将结合联合收割机的新方法，利用 深度测序、高通量细胞筛选、基因组学、基因编辑和细胞功能测试 系统和动物模型来改变我们对人类淋巴细胞分化和功能的理解， 并为受影响的个体创造新的个性化治疗方法。本计划的项目和核心 将通过整合，解决阻碍实现这一转变的主要挑战， 来自T细胞不足患者的临床数据，利用领导者的专业知识进行基础研究， 免疫学、生物信息学、靶标验证和基因组编辑。人类参与者和测序 核心（核心C）在整个计划中发挥重要作用，即（i）招募人类受试者，以及（ii） 进行深度测序研究受试者将是T细胞功能不全或重度 联合免疫缺陷（SCID），尽管有已知的基因，但其基因诊断未经证实 负责调查这些情况。家长也将被录取。核心C将是切入点， 跟踪中心：知情同意、接收样本以及收集和记录表型数据（目标1）; 为所有项目和核心开展的研究准备样本（目标2）; 样本，包括来自项目2和3的SCID患者的CD 34+原代细胞（目标3）。核心C 将获得所有项目（目标2）的基因组DNA和细胞亚群RNA测序，并在允许的情况下与 国家数据库，以促进公开提供关于罕见疾病的去识别信息（目标4）。

CORE C, Human Participants and Sequencing: ABSTRACT The past decade has seen a rapid increase in diagnosis of genetic primary immunodeficiencies (PIDs) involving T lymphocyte dysfunction, in part due to the advent of population based newborn screening for severe combined immunodeficiency (SCID). This Program Project will combine new approaches that utilize deep sequencing, high-throughput cellular screening, genomics, gene editing, and functional testing in cellular systems and animal models to transform our understanding of human lymphocyte differentiation and function, and to create new, personalized treatments for affected individuals. The Projects and Cores of this Program will address the major challenges that have stood in the way of realizing this transformation by integrating clinical data from T-cell insufficient patients with basic investigations drawing on the expertise of leaders in immunology, bioinformatics, target validation, and genome editing. The Human Participants and Sequencing Core (Core C) serves the essential roles for the entire Program of (i) enrolling the human subjects, and (ii) conducting the deep sequencing. Subjects to be studied will be patients with T cell insufficiency or severe combined immunodeficiency (SCID) whose genetic diagnosis is unproven despite having had known genes responsible for these conditions investigated. Parents will be enrolled also. Core C will be the entry point and tracking hub for: informed consent, receiving samples, and collecting and recording phenotypic data (Aim 1); preparing samples for studies to be carried out by all the Projects and Cores (Aim 2); and obtaining special samples, including CD34+ primary cells from SCID patients for Projects 2 and 3 (Aim 3). Furthermore, Core C will obtain genomic DNA and cell-subset RNA sequencing for all Projects (Aim 2), sharing it, as permitted, with national databases to contribute to publicly available de-identified information on rare diseases (Aim 4).